This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Pilot Project Abstract Emerging evidence suggests that vitamin D (VD) may exert a protective effect on the cardiovascular system (CV). Recently, a strong association between low serum VD levels and cardiovascular disease (CVD) has been documented. We performed a cross sectional analysis of data from adults with available data from the NHANES III survey. We found a significant association between low levels of VD and CVD. Importantly, 80% of African Americans fall below the VD median values, and in an adjusted analysis African Americans were seven times and Hispanics three times more likely than Whites to have VD deficiency. Thus, the clinical importance as a disparity issue is highly relevant. Our initial studies show that VD has a promising anti-fibrotic effect on mesenchymal multipotent cells. Using heart derived cells and an animal model of cardiac fibrosis, this project will investigate the basic mechanisms, by which VD enhances cardiac differentiation and protects against CVD, In Aim 1, we will first determine whether supplementation of VD on pre-incubated cardiac derived cells (CDC) with pro-fibrotic factors, reduces fibrosis by inducing an anti-fibrotic phenotype through activation of the vitamin D receptor (VDR), which in turns decreases collagen deposition. In Aim 2, we will next determine whether supplementation of VD on CDC inhibits cell proliferation and enhances cardiac cell differentiation through modulation of the Wnt signaling pathway and through a general down-regulation of key cell cycle related genes. Lastly, in Aim 3, we will investigate the role of VD on the "in vivo" protection against the development of myocardial disarray and interstitial fibrosis observed in a genetically modified mouse model. We are confident that the results generated in this pilot project will provide important insights into natural interventions for CVD prevention and early treatment, as well as future targets such as specific VD metabolites and VD analogs.